Unraveling the potential of Morinda officinalis oligosaccharides as an adjuvant of escitalopram in depression treatment and exploring the underlying mechanisms.

ETHNOPHAMACOLOGICAL RELEVANCE: Morinda officinalis oligosaccharides (MOs) is a mixture of oligosaccharides extracted from the roots of Morinda officinalis (MO). It is approved by Chinese Food and Drug Administration (CFDA) for depression treatment. MOs could improve the antidepressant efficacy of escitalopram in clinic. AIM OF THE STUDY: We aim to explore the antidepressant activity and potential mechanism of the combination usage of MOs and escitalopram on animal model of depression. MATERIALS AND METHODS: Depressive animal model was induced by chronic mild stress (CMS). Behavioral tests were conducted to evaluate the antidepressant efficacy of MOs and escitalopram. Serum neurotransmitter levels were detected by High-performance liquid chromatography (HPLC). Quantitative real-time PCR and Western blotting were applied to assay the hippocampus neurotrophic factors' mRNA and protein levels. Peripheral cytokines levels were measured through Enzyme-Linked Immunosorbent Assay (ELISA). Micorglia polization phenotype was assayed by immunofluorescence and flow cytometry. RESULTS: MOs and escitalopram obviously attenuated depression-like behaviors of CMS mice. Importantly, MOs plus escitalopram exhibited better antidepressant activity on CMS mice than monotherapy. At the same time, MOs combined escitalopram treatment significantly increased hippocampus neurotransmitters and neurotrophic factor levels, stimulated hippocampus neurogenesis and relieved central nervous system (CNS) microglia over-activation of CMS mice. The combination therapy had greater effect on neuroprotection and inflammation attenuation of CMS mice than monotherapy. CONCLUSION: Our results indicates MOs combined escitalopram might produce antidepressant activity through protecting neuron activity, relieving inflammation and modulating microglia polarization process.

Association between the HHEX polymorphism and delayed memory in first-episode schizophrenic patients.

The hematopoietically-expressed homeobox gene (HHEX) played a critical role in regulating the immune system that the abnormality of which was involved in the psychopathology and cognitive deficits of psychiatric disorders. The aim of this study was to investigate the effect of HHEX rs1111875 polymorphism on the susceptibility and cognitive deficits of first-episode schizophrenic patients (FSP). We assessed cognitive function in 239 first-episode patients meeting DSM-IV for schizophrenia, and 368 healthy controls using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The HHEX rs1111875 polymorphism was genotyped. Our results showed that the allelic and genotypic frequencies of HHEX rs1111875 polymorphism didn't differ between FSP and healthy controls (both p > 0.05) after adjusting for sex and age. Cognitive test scores in FSP were significantly lower than those in healthy controls on all scales (all p < 0.001) except for the visuospatial/constructional score (p > 0.05) after adjusting for covariates. There was a significant genotype (p < 0.05) rather than genotype × diagnosis (p > 0.05) effect on the delayed memory score after adjusting for covariates. The HHEX rs1111875 polymorphism was significantly associated with the delayed memory score in FSP (p < 0.05), but not in healthy controls (p > 0.05) after adjusting for covariates. Our findings supported that the HHEX rs1111875 polymorphism did not contribute to the susceptibility to FSP. However, this polymorphism might influence the delayed memory in FSP. Moreover, FSP had poorer cognitive function than healthy controls except for the visuospatial/constructional domain.

Association between increased serum interleukin-8 levels and improved cognition in major depressive patients with SSRIs.

BACKGROUND: The effect of neuroinflammatory cytokines on cognitive deficits in patients with major depressive disorder (MDD) can be altered by selective serotonin reuptake inhibitors (SSRIs). This study aimed to examine serum interleukin-8 (IL-8) levels, cognitive function, and their associations in MDD patients with SSRIs. METHODS: Thirty SSRI-treated MDD patients and 101 healthy controls were recruited for this study. We examined cognitive performance using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum IL-8 levels using the Human Inflammatory Cytokine Cytometric Bead Array in both cases and controls. RESULTS: The RBANS test scores were significantly lower in MDD patients with SSRIs than in healthy controls after controlling for covariates (all p < 0.001). Serum levels of IL-8 were higher in MDD patients with SSRIs than in healthy controls after adjusting for covariates (F = 3.82, p = 0.05). Serum IL-8 levels were positively correlated with sub-scores of delayed memory (r = 0.37, p = 0.04) and visuospatial/constructional (r = 0.43, p = 0.02) in MDD patients with SSRIs but not in in healthy controls (delayed memory score: r = -0.12, p = 0.24; visuospatial/constructional score: r = 0.02, p = 0.81). CONCLUSIONS: Our findings suggested that increased serum IL-8 level might not only be involved in the MDD psychopathology or the use of SSRIs but also correspond to improving MDD delayed memory and visuospatial/constructional function.

Morinda officinalis oligosaccharides mitigate chronic mild stress-induced inflammation and depression-like behaviour by deactivating the MyD88/PI3K pathway via E2F2.

Morinda officinalis oligosaccharides (MOs) are natural herbal extracts that have been shown to exert antidepressant effects. However, the mechanism of this effect remains unclear. Here, we explored the mechanism by which MOs improved experimental depression. Using a chronic mild stress (CMS) murine model, we examined whether MOs could protect against depressive-like behaviour. Lipopolysaccharide (LPS)- and ATP-treated BV2 cells were used to examine the potential mechanism by which MOs mediate the inflammatory response. We found that MOs prevented the CMS-induced reduction in the sucrose preference ratio in the sucrose preference test (SPT) and shortened the immobility durations in both the tail suspension test (TST) and forced swim test (FST). We also noticed that MOs suppressed inflammatory effects by deactivating the MyD88/PI3K pathway via E2F2 in CMS mice or LPS- and ATP-stimulated BV2 cells. Furthermore, overexpression of E2F2 blunted the beneficial effects of MOs in vitro. Collectively, these data showed that MOs exerted antidepressant effects in CMS mice by targeting E2F2-mediated MyD88/PI3K signalling pathway.

Associations of decreased serum total protein, albumin, and globulin with depressive severity of schizophrenia.

Objective: Depression and schizophrenia (SCH) were accompanied by an acute phase response (APR) that was implicated in the alterations in total protein (TP), albumin, and globulin levels. The aims of this study are to examine serum TP, albumin, globulin levels, depressive symptoms, and their associations in patients with SCH. Methods: We recruited 34 patients with SCH and 136 healthy controls (HCs) according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Psychiatric symptoms and biomarkers were assessed using the Chinese version of the Positive and Negative Syndrome Scale (PANSS) as well as the bromocresol green and biuret methods. Results: Serum TP (F = 46.11, p < 0.001, η2 = 0.19), albumin (F = 31.69, p < 0.001, η2 = 0.14), and globulin (F = 12.48, p < 0.001, η2 = 0.06) levels were lower in patients than those in HCs after adjusting for covariates. Serum TP (r = -0.37, p = 0.03) and albumin (r = -0.37, p = 0.03) levels were negatively correlated with depressive score in patients. Stepwise multivariate regression analysis showed the negative associations of depressive score with serum TP (ß = -0.13, t = -2.92, p = 0.007), albumin (ß = -0.23, t = -2.36, p = 0.03), and globulin (ß = -0.16, t = -2.40, p = 0.02) levels in patients. Serum TP, albumin, and globulin levels exhibited the accuracies of 87.1, 70.0, and 69.4% in discriminating between patients and HCs (area under the curve [AUC]: 0.78, 0.68, and 0.77; sensitivity/specificity: 52.9%/95.6%, 55.9%/73.5%, and 76.5%/67.6%). Conclusion: Our data suggested that decreased serum TP, albumin, and globulin should be regarded as the SCH risk factors and were implicated in the depressive severity of SCH, which further provided the support for the hypothesis that SCH and depression were accompanied by the abnormal inflammatory cytokines with the APR.

The type 2 diabetes mellitus susceptibility gene CDKAL1 polymorphism is associated with depressive symptom in first-episode drug-naive schizophrenic patients.

BACKGROUND: Patients with schizophrenia have an increased prevalence of type 2 diabetes mellitus that has shown a significant association with the rs7754840 polymorphism in the gene encoding the cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 (CDKAL1). OBJECTIVE: To examine whether this polymorphism was involved in the susceptibility in first-episode drug-naive schizophrenic patients (FDSP), and further influenced their clinical symptoms. METHODS: This polymorphism was genotyped in 239 FDSP and 368 healthy controls. The clinical symptoms in FDSP were assessed using the Positive and Negative Syndrome Scale (PANSS) five-factor models. RESULTS: There was no significant difference in the allelic and genotypic frequencies of this polymorphism between two groups (both p > 0.05) after adjusting for covariates. However, the PANSS depressive score significantly differed by genotype in FDSP after adjusting for covariates (F = 5.25, p = 0.006). This significant difference also persisted after Bonferroni correction (p < 0.05). FDSP with C/C genotype had significantly higher PANSS depressive score than those with C/G genotype (p = 0.007) and those with G/G genotype (p = 0.005). Moreover, further stepwise multivariate regression analysis showed the significant association between the rs7754840 polymorphism and PANSS depressive score in FDSP (ß = -1.07, t = -2.75, p = 0.007). CONCLUSIONS: Our findings demonstrated that although the CDKAL1 rs7754840 polymorphism did not contribute to the susceptibility to FDSP, it might be implicated in depressive symptoms in this patient group.

Association between stereopsis deficits and attention decline in patients with major depressive disorder.

Cognitive and sensory deficits were considered a core feature of major depressive disorder (MDD). However, few studies investigated stereopsis integrity in patients with MDD. Thus, the objectives of this study investigated stereopsis integrity and its correlations with cognitive function and depressive symptom in patients with MDD. 90 patients with MDD and 116 healthy controls (HCs) were enrolled in this study. Their stereoacuity was evaluated using the Titmus Stereopsis Test as well as assessing their cognitive function and depressive symptom by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Hamilton Depression Scale (HAMD). Log seconds of arc was significantly higher in patients than HCs (1.92 ± 0.41 versus 1.67 ± 0.16, t = 5.35, p < 0.0001). The percentage of patients with correct stereopsis detection was markedly declined in 400 (z = 3.06, p = 0.002), 200 (z = 3.84, p < 0.001), 140 (z = 4.73, p < 0.001), 100 (z = 4.58, p < 0.001), 80 (z = 5.06, p < 0.001), 60 (z = 4.72, p < 0.001), 50 (z = 4.24, p < 0.001), and 40 (z = 4.85, p < 0.001) seconds of arc compared with HCs. Log seconds of arc was significantly correlated with the RBANS total score (r = -0.38, p < 0.0001), subscores of attention (r = -0.49, p < 0.0001) and language (r = -0.33, p = 0.001) rather than HAMD score (r = 0.03, p = 0.78) in MDD patients. In addition, log seconds of arc was significantly related to the RBANS total score (r = -0.58, p < 0.0001) and language score (r = -0.45, p = 0.006) rather than attention score (r = -0.30, p = 0.07) in HCs. Further stepwise multivariate regression analyses showed the negative correlation of log seconds of arc with attention score (ß = -0.80, t = -3.95, p < 0.0001) rather than HAMD score (ß = -0.008, t = -0.09, p = 0.93) in MDD patients. However, there was no relationship between log seconds of arc and attention score in HCs (ß = 1.52, t = 1.19, p = 0.24). Our results identified the marked deficits of stereopsis in MDD patients that were tightly correlated with their attention functioning rather than depressive symptom.

Associations among gonadal hormone, triglycerides and cognitive decline in female patients with major depressive disorders.

BACKGROUND: Cognitive impairment has been identified as a core feature of depression. Serum triglycerides (TG), gonadal hormone and sex difference were shown to influence cognitive performance. The purpose of this study was to investigate the associations among serum TG, gonadal hormone, sex difference and cognitive performance in patients with major depressive disorders (MDD). METHODS: The enrolled 183 patients (male/female = 80/103) meeting DSM-IV criteria for MDD were divided into high TG group (patients-HTG) and normal TG group (patients-NTG) according to TG level. Serum TG, estradiol (E2) and testosterone (T) levels were measured by the glycerokinase peroxidase-peroxidase and chemiluminescence methods. Cognition was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The study was conducted between August 2016 and January 2020. RESULTS: In female, patients-HTG had lower immediate memory, language, attention, delayed memory and RBANS total scores than patients-NTG after adjusting for covariates. There were significant differences in serum E2 and T levels between patients-HTG and patients-NTG in female after controlling for covariates. In female patients-HTG, serum E2 level was positively associated with immediate memory, delayed memory and RBANS total scores, and serum T level was positively related to immediate memory, language and RBANS total scores. These findings were not seen in male patients. CONCLUSIONS: Our data suggested that patients-HTG exhibited poorer cognitive function compared with patients-NTG in female. Moreover, the decline in serum gonadal hormone level might contribute to the high TG development of female MDD, and was further implicated in their cognitive decline.

The role of lipoprotein profile in depression and cognitive performance: a network analysis.

Lipid profile (total cholesterol and lipoprotein fractions) has been found to correlate with depression and cognitive impairment across the lifespan. However, the role of lipid levels in self-rated depressive state and cognitive impairment remains unclear. In this study, we examined the relationship between lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol) and cognition in adults with and without self-rated depression. Four hundred and thirty-eight healthy participants completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Self-Rating Depression Scale (SDS), and a serum lipoprotein test. Using multivariate ANOVA, partial correlation and network analysis, a network linking lipoprotein profile, depressive state and cognition was constructed. A significant difference in serum lipid profile between the high and low depressive groups was detected. Depressive state had a strong negative correlation with cognitive performance. Of the lipid profile, only high-density lipoprotein was positively correlated with depressive symptom severity, whereas the other three indices showed negative correlation with both depressive state and cognitive performance. Our results suggest that serum lipid profile may be directly linked to self-rated depression and cognitive performance. Further studies recruiting larger clinical samples are needed to elucidate the specific effect of lipoprotein on cognitive impairment in mood disorder.

Association between dopamine beta-hydroxylase polymorphism and attention function in suicide attempters with chronic schizophrenia.

BACKGROUND: Patients with schizophrenia are at a higher risk for suicide compared with the general population. Dopamine beta-hydroxylase (DßH) plays a key role in the conversion of dopamine to norepinephrine, which is related to suicidal behavior and cognitive regulation. OBJECTIVE: To examine whether there is the effect of DßH 5'-insertion/deletion (Ins/Del) polymorphism on cognitive performance in suicide attempters with chronic schizophrenia. METHODS: This polymorphism was detected in 114 suicide attempters and 617 non-suicide attempters with chronic schizophrenia. Cognitive performance was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RESULTS: The allelic and genotypic frequencies of this polymorphism between two groups did not differ after controlling for covariates (both, p > .05). There were no differences in RBANS scores between two groups after adjusting for covariates (all, p > .05). However, based on the genotype grouping in suicide attempters and non-attempters, the attention score significantly differed after adjusting for covariates (both, p < .05). Further analysis indicated that this polymorphism was associated with attention score in suicide attempters (p < .05), but not in non-suicide attempters (p > .05). CONCLUSIONS: DßH 5'-Ins/Del polymorphism was not a risk locus of suicide attempters, but it was implicated in attention regulation in suicide attempters with chronic schizophrenia.

Prevalence, social-demographic and cognitive correlates of depression in Chinese psychiatric medical staff.

BACKGROUND: The high prevalence of depression in general population was related to its social-demographics and cognitive performance. However, no studies investigated the prevalence of depression, its social-demographic and cognitive correlates in psychiatric medical staff. Thus, the aims of this study investigated the prevalence, social-demographic and cognitive correlates of depression in Chinese psychiatric medical staff. METHODS: 186 Chinese psychiatric medical staff were enrolled in Wenzhou Kangning Hospital. Depressive symptom score was assessed by the Self-rating Depression Scale (SDS). Cognition was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RESULTS: The prevalence of depression was 17.74% in these medical staff. The RBANS total score in participants with depressive symptom was significantly lower than that in participants with not depressive symptom after controlling for the confounding variables. The Person correlation analysis found that the normal SDS score in these medical staff was significantly related to age, education, occupations, RBANS total score and subscale scores. Stepwise multivariate regression analysis further identified that age and RBANS total score were significantly associated with the normal SDS score in these medical staff. LIMITATIONS: The limitations included cross-sectional study design, the small sample size, and the self-rating scale of depression. CONCLUSIONS: The prevalence of depression in Chinese psychiatric medical staff was higher in comparison with Chinese general population, but lower in comparison with Chinese medical staff. Cognitive deficits might be considered a core feather of depression that should be a valuable target for future interventions. Age influenced depressive symptom in these medical staff .

Association between decreased HDL levels and cognitive deficits in patients with bipolar disorder: a pilot study.

BACKGROUND: Cognitive deficits are common in patients with bipolar disorder (BD). Abnormal high density lipoprotein (HDL) levels have been implicated in cognitive deficits associated with ageing and neurodegenerative disorders. The present study aimed to investigate serum HDL levels, cognitive deficits and their association in patients with BD. METHODS: Thirty-seven patients with BD and 37 gender- and age-matched healthy controls (HCs) were recruited in a case-control study. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and serum HDL levels were measured using enzymatic colourimetry. RESULTS: There was no difference in serum HDL levels between patients with BD and HCs after adjusting for gender, age, education and body mass index (BMI). Cognitive test scores in patients with BD were significantly lower than those in HCs except for the visuospatial/constructional index after adjusting for confounding variables. Serum HDL levels were positively correlated with RBANS total score and language score in patients with BD. Stepwise multiple regression analysis showed that serum HDL levels were significantly correlated with RBANS total score and subscale scores on immediate memory and language in patients with BD after adjusting for confounding factors. CONCLUSIONS: Our findings suggest that patients with BD had poorer cognitive performance than HCs except for the visuospatial/constructional domain, and decreased serum HDL levels were correlated with cognitive deficits, especially in immediate memory and language domains in patients with BD.

Cognitive Impairments in First-Episode Drug-Naïve Versus Medicated Depressive Patients: RBANS in a Chinese Population.

Cognitive deficits are a core feature of major depressive disorder (MDD). However, there are no previous studies that directly compare cognitive performance between first-episode drug-naive depressive patients (FDDP) and medicated depressive patients (MDP). Therefore, the aim of this study was to investigate whether there were the differences in cognitive functions between FDDP and MDP. Sixty-two FDDP, 111 MDP and 90 healthy controls were enrolled in a Chinese population. Cognitive functions were assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). There were the differences in the RBANS total score (F = 26.55, p < 0.001), subscales of immediate memory (F = 3.95, p = 0.02), language (F = 54.11, p < 0.001) and delayed memory (F = 11.19, p = 0.001) among the three groups after controlling for gender, education, smoking and body mass index (BMI). These differences in the RBANS total score, subscales of language and delayed memory passed the Bonferroni corrections (all, p < 0.05). Compared to healthy controls, FDDP and MDP had poorer cognitive performance including the RBANS total score, and subscales of language and delayed memory (all, p < 0.05) after controlling for the variables. FDDP experienced greater language deficits than MDP (p < 0.05) after controlling for the variables. Education was correlated with the language score in FDDP (r = 0.61, p < 0.001). Multivariate regression analysis indicated that education was an independent contributor to the language score in FDDP (ß = 3.11, t = 5.48, p < 0.001). Our findings indicated that FDDP had poorer language performance than MDP. Moreover, education could influence the language performance in FDDP.

Association between decreased serum TBIL concentration and immediate memory impairment in schizophrenia patients.

Cognitive impairment is a core feature of schizophrenia (SCH). In addition to the toxic effect of Bilirubin (BIL), it has antioxidant properties that were associated with the psychopathology and cognitive impairment of psychiatric disorders. The aim of this study was to examine the correlation of serum total BIL (TBIL) concentration with cognitive impairment in SCH patients. We recruited 34 SCH patients and 119 healthy controls (HCs) in this case-control design. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Serum TBIL concentration was measured using the immunoturbidimetric method. Serum TBIL concentration was significantly decreased in SCH patients compared to HCs after adjusting for age, gender, and education. Serum TBIL concentration in SCH patients was also positively correlated with the RBANS immediate memory score. Further stepwise multiple regression analysis confirmed the positive association between serum TBIL concentration and immediate memory score in SCH patients. Our findings supported that the decline in serum TBIL concentration was associated with the immediate memory impairment and psychopathology of SCH.

Association between decreased serum albumin levels and depressive symptoms in patients with schizophrenia in a Chinese Han population: A pilot study.

Albumin is a metal-binding protein with free-radical scavenging properties and is recognized as a vital antioxidant. Moreover, an excess of free radicals may contribute to depressive symptoms and the psychopathology of psychiatric disorders. This study examined serum albumin levels, depressive symptoms, and their association in patients with schizophrenia. Thirty-four patients with schizophrenia (diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition) and 136 healthy controls were consecutively enrolled in this case-control study. The clinical psychiatric symptoms in patients with schizophrenia were assessed using the Positive and Negative Syndrome Scale (PANSS). Serum albumin levels were measured in all participants using an immunoturbidimetric method. This study was conducted between 2016 and 2017. Serum albumin levels were significantly lower in patients with schizophrenia compared to healthy controls after adjusting for gender, age and education (F = 16.04, p = 0.000). Serum albumin levels were negatively correlated with the depressive score of PANSS in patients with schizophrenia (r = -0.37, p = 0.03). Additionally, a further stepwise multivariate regression analysis showed that serum albumin levels were significantly associated with the depressive score of PANSS in patients with schizophrenia (ß = -0.37, t = -2.25, p = 0.03). Our data suggested that decreased serum albumin levels may contribute to the psychopathology of schizophrenia and that a decline in serum albumin levels was associated with the severity of depressive symptoms in patients with schizophrenia.

Arsenic Trioxide Inhibits Cell Growth and Invasion via Down- Regulation of Skp2 in Pancreatic Cancer Cells.

Arsenic trioxide (ATO) has been found to exert anti-cancer activity in various human malignancies. However, the molecular mechanisms by which ATO inhibits tumorigenesis are not fully elucidated. In the current study, we explored the molecular basis of ATO-mediated tumor growth inhibition in pancreatic cancer cells. We used multiple approaches such as MTT assay, wound healing assay, Transwell invasion assay, annexin V-FITC, cell cycle analysis, RT-PCR and Western blotting to achieve our goal. We found that ATO treatment effectively caused cell growth inhibition, suppressed clonogenic potential and induced G2-M cell cycle arrest and apoptosis in pancreatic cancer cells. Moreover, we observed a significant down-regulation of Skp2 after treatment with ATO. Furthermore, we revealed that ATO regulated Skp2 downstream genes such as FOXO1 and p53. These findings demonstrate that inhibition of Skp2 could be a novel strategy for the treatment of pancreatic cancer by ATO.